文献类型：期刊文献

中文题名：基于AMPK/GLUT4信号通路探讨红芪多糖对糖尿病胃轻瘫脾气虚证大鼠小肠平滑肌糖代谢的影响

英文题名：Discussion on the Effects of Hedysarum Polybotrys Polysaccharide on Glucose Metabolism of Small Intestinal Smooth Muscle in Diabetic Gastroparesis Rats with Spleen Qi Deficiency Syndrome Based on AMPK/GLUT4 Signaling Pathway

作者：王文雯[1,2];仲子惠[1,2];万生芳[1];马欣欣[1];张磊[1];刘苗[1];荀敏奇[1];李瑾瑜[1];冯康[1]

第一作者：王文雯

机构：[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2025

卷号：32

期号：8

起止页码：91

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

基金：国家自然科学基金(82060914)。

语种：中文

中文关键词：红芪多糖;糖尿病胃轻瘫;脾气虚证;AMPK/GLUT4信号通路;糖代谢;大鼠

外文关键词：Hedysarum Polybotrys polysaccharide;diabetic gastroparesis;spleen qi deficiency syndrome;AMPK/GLUT4 signaling pathway;glucose metabolism;rats

摘要：目的观察红芪多糖对糖尿病胃轻瘫(DGP)脾气虚证大鼠小肠平滑肌糖代谢的影响,基于AMPK/GLUT4信号通路探究其作用机制。方法72只雄性Wistar大鼠随机分为空白组12只、造模组60只,造模组腹腔注射链脲佐菌素+高脂高糖饲料不规则喂养联合游泳力竭法复制DGP脾气虚证模型。将成模大鼠随机分为模型组、二甲双胍组和红芪多糖高、中、低剂量组。二甲双胍组予盐酸二甲双胍100 mg/kg灌胃,红芪多糖高、中、低剂量组分别予红芪多糖200、100、50mg/kg灌胃,空白组和模型组灌胃纯净水,每日1次,连续8周。检测大鼠胃排空率、小肠推进率,HE染色观察胃窦、回肠组织平滑肌形态,免疫荧光染色检测回肠组织胰高血糖素样肽-1(GLP-1)表达,ELISA检测血清脂联素(APN)、胰高血糖素(Glu)、胰岛素(INS)含量,Western blot检测回肠组织葡萄糖转运蛋白(GLUT)4、GLUT1、腺苷酸活化蛋白激酶(AMPK)、p-AMPK蛋白表达。结果与空白组比较,模型组大鼠随机血糖明显升高,体质量、胃排空率、小肠推进率均明显降低(P<0.01),胃窦组织黏膜下层水肿,结缔组织排列疏松,少量淋巴细胞、粒细胞和巨噬细胞浸润,回肠组织杯状细胞数量减少,肠绒毛上皮细胞脱落,与固有层间隙增宽,回肠组织GLP-1表达明显降低(P<0.05),血清APN、INS含量明显降低,Glu含量明显升高(P<0.01),回肠组织GLUT4、p-AMPK/AMPK蛋白表达明显降低,GLUT1蛋白表达明显升高(P<0.01);与模型组比较,二甲双胍组和红芪多糖高剂量组大鼠随机血糖降低,体质量、胃排空率、小肠推进率升高(P<0.05,P<0.01),胃窦组织细胞排列较规则、脱落减少,水肿减轻,回肠组织平滑肌结构较完整,细胞分布均匀,炎性细胞浸润减少,回肠组织GLP-1表达升高,血清APN、INS含量升高,Glu含量降低,回肠组织GLUT4、p-AMPK/AMPK蛋白表达升高,GLUT1蛋白表达降低(P<0.05,P<0.01)。结论红芪多糖可能通过激活AMPK上调GLUT4、下调GLUT1表达,促进小肠平滑肌对葡萄糖的摄取利用,改善DGP脾气虚证大鼠糖代谢。
Objective To observe the effects of Hedysarum Polybotrys polysaccharide(HPS)on the glucose metabolism of small intestinal smooth muscle in rats with diabetic gastroparesis(DGP)of spleen qi deficiency syndrome;To explore its mechanism based on AMPK/GLUT4 signaling pathway.Methods Totally 72 male Wistar rats were randomly divided into 12 in the blank group and the remaining 60 rats were assigned to the model group.The DGP spleen qi deficiency syndrome model was replicated by intraperitoneal injection of streptozotocin+irregular feeding with high-fat and high sugar feed combined with swimming exhaustion method.The model rats were randomly divided into model group,metformin group and HPS high,medium-and low-dosage groups.The metformin group was given 100 mg/kg metformin hydrochloride by gavage,while the HPS high-,medium-and low dosage groups were given 200,100 and 50 mg/kg HPS by gavage,respectively.The blank group and model group were given purified water by gavage once a day for 8 consecutive weeks.The gastric emptying rate and small intestine propulsion rate in rats were detected,HE staining was used to observe the smooth muscle morphology of gastric antrum and ileal tissue,immunofluorescence staining was used to detect the expression of glucagon like peptide-1(GLP-1)in ileal tissue,ELISA was used to detect the contents of adiponectin(APN),glucagon(Glu)and insulin(INS)in serum,Western blot was used to detect the protein expressions of glucose transporter(GLUT)4,GLUT1,AMP-activated protein kinase(AMPK)and p-AMPK in ileal tissue.Results Compared with the blank group,the model group rats showed significantly increased random blood glucose,significantly decreased body mass,gastric emptying rate and small intestinal propulsion rate(P<0.01);the edema in the submucosal layer,loose arrangement of connective tissue,infiltration of a small number of lymphocytes,granulocytes and macrophages,reduced number of goblet cells in the ileal tissue,shedding of intestinal villous epithelial cells and widening of the gap between the submucosal layer and the lamina propria;the expression of GLP-1 in ileal tissue was significantly decreased(P<0.05),the contents of serum APN and INS were significantly decreased,and the content of Glu significantly increased(P<0.01),the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue were significantly decreased,while the expression of GLUT1 protein significantly increased(P<0.01).Compared with the model group,rats in metformin group and HPS high-dosage group showed a random decrease in blood glucose,an increase in body mass,gastric emptying rate,and small intestine propulsion rate(P<0.05,P<0.01);a more regular arrangement of gastric antral tissue cells,a reduction of shedding cells and edema,the smooth muscle structure of the ileal tissue was relatively intact,with evenly distributed cells and reduced infiltration of inflammatory cells;the expression of GLP-1 in ileal tissue increased,the contents of serum APN and INS increased,and the content of Glu decreased,the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue increased,while the expression of GLUT1 protein decreased(P<0.05,P<0.01).Conclusion HPS may up-regulate GLUT4 and down-regulate GLUT1 expression through activates AMPK,promotes glucose uptake and utilization by small intestinal smooth muscle,and improves glucose metabolism of DGP rats with spleen qi deficiency syndrome.